Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact patho-physiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause.

Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications.

Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT1b/1d agonists (the ‘triptans’) and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids.

Frequent, severe and long-lasting migraine attacks require prophylaxis. Established drugs used for the prevention of migraine such as β-adrenoceptor antagonists (β-blockers), calcium channel antagonists, antidepressants and others have an unknown mode of action in migraine. Their prophylactic effect in migraine was discovered by chance in clinical practice when these drugs were used for other purposes. Recently, research into the mechanisms of migraine and the progressive recognition that cortical hyperexcitability and an imbalance between neuronal inhibition [mediated by γ-aminobutyric acid (GABA)] and excitation (mediated by excitatory amino acids) may play an important role in migraine pathophysiology have lead to the identification of potential new agents for the prevention of migraine attacks. This paper reviews the recent literature on these new agents.

A search was conducted using MEDLINE from 1998 to November 2001 with the following search terms: migraine, preventive, prophylactic and treatment. Headache textbooks edited in 2000 and 2001 were also used.

After analysing the available controlled and uncontrolled clinical studies as well as abstracts, divalproex sodium (valproate semisodium) can be recommended for the prevention of migraine. Lamotrigine may be useful for preventing aura associated with migraine, and topiramate seems a promising option pending trials with more patients, which are currently underway. Riboflavin (which is possibly involved in improving neuronal energy production) appears to be a promising agent, although comparisons with established prophylactic medications are needed. Gabapentin, magnesium, lisinopril and botulinum toxin A have recently been suggested to be effective; however, at present, there are insufficient rigorous and reliable controlled data on these drugs for them to be indicated for such use. Emerging options such as tiagabine, levetiracetam, zonisamide and petasites may all be useful, but controlled data are required to confirm their efficacy. The anti-asthma medication montelukast was found to be effective in an open trial, but ineffective in a recently completed controlled trial.

There is an expectation that modern neuroscience will soon provide more efficacious and better tolerated prophylactic medications for migraine.

Migraine is a highly prevalent, chronic, episodic condition. The direct and indirect costs of migraine have a large economic impact. Research has shown that migraine abortive medications reduce healthcare costs, improve health-related quality of life, decrease migraine disability and keep patients effective in the workplace. This class of medications, therefore, has a clearly defined role within a disease management program. However, the role of prophylactic medications in terms of costs and patient-focused outcomes within a disease management program has not been clearly defined.

Based on a review of the US Headache Consortium Evidence-Based Treatment Guidelines and an examination of issues surrounding prophylactic medications, we conclude that the role of preventive therapy in terms of costs and patient-focused outcomes is not clearly defined. Currently, there are insufficient data available to assess the impact of migraine prophylactic therapy on costs and patient-focused outcomes. Hence, it is premature to state the precise role of preventive therapy in a migraine disease management program. Additional research is needed to better delineate the criteria for migraine prophylaxis, to validate clinical efficacy studies of preventive therapy, to determine the cost-effectiveness of prophylactic therapy, and to determine the effect of preventive therapy on patients’ health resource use, health-related quality of life, and lost productivity.

Clinical trials of therapies for acute migraine attacks have evolved over the years from open-label, small observational studies to highly structured randomised, controlled trials. The International Headache Society Committee on Clinical Trials in Migraine developed a tool to guide in designing scientifically sound trials. The proof of effect is best achieved in a clinical trial with: (i) clearly defined objectives; (ii) a well-characterised study population, identified using well-validated diagnostic tools; (iii) proper randomisation and blinding; (iv) inclusion of a placebo arm, with proper balancing of patients receiving placebo and those receiving active drug; (v) adequate study power; and (vi) appropriate statistical methods. Roth narallel and crossover studies may be suitable in clinical trials of antimipraine agents, although the latter are a better choice in patient preference and bioequivalence studies.

Although various efficacy measures are used to assess treatment effect, the 2-hour pain free rate (total resolution of pain within 2 hours after an initial moderate to severe headache) is preferred because it is clinically relevant and is relatively ‘placebo-insensitive’. Various migraine surveys have indicated that a rapid onset of therapeutic effect is a highly desirable attribute of an antimigraine drug. Therefore, accurate measurements of treatment effect before 2 hours are becoming increasingly emphasised.

Consistency of effect across multiple attacks adds to the understanding of the therapeutic efficacy of a test drug. Finally, preference and satisfaction studies allow us to assess patients’ global impression of a particular treatment, weighing the positive effects on pain and associated symptoms of migraine against potential adverse effects.

Migraine is a common, temporarily disabling, episodic disorder that affects about 28 million adults in the United States [1]. The World Health Organization classified a severe migraine attack requiring bed rest as one of the most disabling of the 30 diseases considered [2]. However, even between attacks, migraineurs live in fear that the next attack could disrupt their work, social, or family responsibilities. Thus, there is likely to be some large, but unstudied, chronic disability associated with migraine even between attacks.

Behavioral interventions, particularly biofeedback and relaxation therapy, have demonstrated their effectiveness in the treatment of both adults and older children with migraine in controlled trials. The physiological basis for their effectiveness is unclear, but data from one trial suggest that levels of plasma β-endorphin can be altered by relaxation and biofeedback therapies. The data supporting the effectiveness of behavioral therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment. This is due in part to methodological issues, especially the lack of a specific test for migraine, which has hampered research and helped lead to an inappropriate de-emphasis on care for childhood headache. In addition, migraine headaches in children are often briefer and have a higher rate of spontaneous remission than those experienced by adults, making it difficult to separate effective from ineffective treatments.

While it is widely believed that stress is a major factor in childhood migraine, well-designed studies have had difficulty developing data to support this viewpoint. Many clinicians utilize ‘confident reassurance’, reassuring the family that the child is not seriously ill, in the belief that having migraine headaches can be stressful. They also modify behaviors that are believed to trigger migraine headaches, such as poor sleep habits or irregular meal times.

Relaxation therapies use techniques such as progressive relaxation, self-hypnosis, and guided imagery. Several studies have found relaxation therapies to be as effective, or more effective, in reducing the frequency of migraine headaches than modest doses of a β-blockade medication, although one study found relaxation therapy to be no more effective than a control program. Several studies have demonstrated that these therapies can be taught to children in a low cost but effective manner.

Biofeedback therapies commonly use an apparatus to demonstrate a physiological effect. Most commonly in pediatrics, children are taught to raise the temperature of one of their fingers. This can be done with or without a thermometer. Several groups have shown that these techniques can be taught to children and that their use is associated with fewer and briefer migraine headaches.

People who experience migraines can also experience episodic headaches throughout life. An important consideration is preparing children to deal with future headaches, allowing them to feel in control of their health. Behavioral therapies have the potential to do this, giving the child access to a technique that can be easily resumed without a medical visit or prescription.

Introduction: Many patients with migraine do not consult a physician, or do not achieve adequate relief after consulting a physician because of undertreatment. The objective of the Migraine and Zomig1. Evaluation study was to provide insights into the management of migraine in the general population.

Methods: In phase I, 5553 members of the general public in the UK, France, Germany, Italy, and the US were interviewed by telephone and classified according to International Headache Society criteria. The Migraine Disability Assessment Scale (MIDAS) questionnaire was used to assess the impact of migraine on work, home and social lives. In phase II, 516 patients with clinically diagnosed migraine were interviewed to assess the impact of migraine on daily life, attitudes towards migraine, perceptions of current treatments and aspirations for future treatments.

Results: In phase I, the average prevalence of migraine over the five countries was 9%. Migraine posed a significant burden in terms of the impact on patients’ daily lives, and attack severity and frequency. However, medical consultation rates were low; reasons for this included patients not recognising that they had migraine or having low expectations about treatment benefits. On average, only 10% of patients who had consulted a physician had been prescribed a triptan. Only 22% of participants in phase II thought that migraine did not markedly affect their lives. In each of the five countries, ≥ 50% of patients required bed rest to manage migraine attacks, demonstrating the impact of migraine-related disability on patients’ lives. Assessment of MIDAS scores confirmed the debilitating effect of migraine; > 50% of respondents had a MIDAS grade of III or IV, indicating moderate or severe disability. Less than one-third of patients reported that their current medication was consistently effective and only 36% were ‘very satisfied’ with their current therapy. High efficacy and rapid pain relief were rated as the most important attributes of migraine medications. When asked which formulation they would like to see more of, most patients chose a tablet that dissolves in the mouth without the need to take liquids.

Conclusions: These results show that migraine patients worldwide are still not receiving adequate treatment and there remains a significant unmet need in migraine care. The challenge for the future is to diagnose migraine early and offer patients effective migraine-specific therapies. Physicians particularly need to reach patients who do not realise they have migraine and those who have lapsed from care.

Migraine is a common, chronic headache disorder affecting about 26 to 28 million Americans. It is notable for the variability of diagnostic testing, therapeutic interventions and costs, as well as high utilization of healthcare resources, its considerable impact on quality of life and its economic impact for both patients and employers. Moreover, there appears to be low patient satisfaction with migraine care, a wide variability in utilization of physician and emergency department services and increasing pharmacy costs for migraine therapies. Standards of care and clinical guidelines for migraine are now available. For these reasons, migraine represents an ideal disorder for a disease management (DM) program.

The suggested steps in developing a DM program for migraine include setting appropriate goals, identifying suitable patients, providing components of care and using continuous quality improvement methods to reach targets.

A DM management program for migraine in a managed care organization which was developed and implemented is overviewed in this article. Medicaid and commercial enrollees were included. Members with migraine who had ≥1 migraine-related encounter(s) in the previous year, or query of the pharmacy claims database for members who filled one or more prescriptions for migraine specific medication(s) during the 12-month period, were eligible. The objectives were: an increased proportion of patients with symptom relief and returning to normal activities within 2 hours after taking medication; taking prophylactic medications (if experiencing ≥3 migraine attacks/month) and reporting knowledge of potential migraine triggers; decreased utilization of emergency care for migraine and increased patient satisfaction with migraine treatment and health plan and /or provider. Improved health-related quality of life and reduced level of migraine-related disability compared with baseline were also anticipated. Patient satisfaction with overall migraine treatment was selected as the primary endpoint in the evaluation of the program.

Early feedback on outcomes from patients and providers has been very positive. There have been no major unexpected problems to date.

There are no great migraine preventives! No migraine preventive agent studied in good randomized, double blind, placebo-controlled trials proved to be 50% better than placebo.

Migraine trials typically focus on episodic migraine, a milder, gentler type of migraine that is selected for low frequency, lack of daily headaches, no preventive need, and previous failure to no more than a few preventive agents. These features are not typical of the usual migraine patient seen in most neurologic practices, thus the results of clinical trials may not carryover to real world situations.

Treatment of frequent, chronic, or pervasive migraine is inadequate, and never has been studied in randomized controlled trials. Traditional migraine preventives, eg, beta-blockers, calcium channel blockers, and tricyclic antidepressants, are often ineffective in difficult or complicated populations.

The antiepileptic drugs represent a category of pharmaceutics that target the neuronal instability and central hyperexcitability of migraine, and, through these actions, may be more effective than traditional preventives.

Episodic migraine attacks are associated with peripheral and central sensitization; however, if attacks are frequent, severe, or long lasting, this sensitization may increase the risk of developing daily headaches.

If antiepileptic drugs have an effect on central sensitization, perhaps mediated via glutamate inhibition or gamma-aminobutyric acid potentiation, it is appropriate to use these agents early in migraine treatment, particularly in the highly comorbid patient, possibly in conjunction with agents that antagonize the 5HT2 receptor.

This report reviews the best currently available evidence on antiepileptic drugs in the prevention of episodic migraine, and tabulates potential drug-drug and cytochrome P450 interactions. All antiepileptic drugs presented are effective in migraine prevention. However, deciding on the best agent for each individual patient will require recognizing comorbidity and assessing antiepileptic drug pharmacodynamics, tolerability, and safety.

Opinion statement

The definition of recurrence includes the following: any headache occurring after a headache-free state at 2 hours and within 24 hours after intake of drug; a headache that has never been studied systematically; a headache that may not be an outcome of drug treatment; a headache that may be due to the inherent nature of migraine and individual patient characteristics such as duration of attack; and headache for which effective treatment may be a re-dose of the initial medication or addition of steroidal or nonsteroidal anti-inflammatory medications.